Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology · 2026
Epithelial histone deacetylase 7 (HDAC7) constitutes a negative feedback loop restraining interleukin (IL)-13-driven eosinophilic inflammation in chronic rhinosinusitis.
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Sun Xiwen, Liu Wenqin, Cui Yueming, Guan Haoyan, Sun Yueqi, Xu Rui
Аннотация
BACKGROUND: Epithelial dysfunction is a central driver of type 2 inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). Although epigenetic mechanisms are known to regulate mucosal immunity, the specific role of histone deacetylase 7 (HDAC7) in modulating the magnitude of epithelial type 2 responses remains unclear. We hypothesized that HDAC7 functions as an inducible checkpoint to restrain excessive inflammation.
OBJECTIVE: To explore the role of epithelial HDAC7 in restraining excessive inflammation in CRSwNP.
METHODS: Primary human nasal epithelial cells were exposed to inflammatory stimuli to identify HDAC7 inducers. Epithelial HDAC7 expression in patient tissues was correlated with inflammatory markers and remodeling indices. Mechanistic roles were assessed using lentiviral knockdown, transcriptome sequencing, and eosinophil chemotaxis assays.
RESULTS: Interleukin (IL)-13 selectively induced epithelial HDAC7 expression. In clinical tissues, lower HDAC7 expression within the CRSwNP cohort correlated with severe type 2 inflammation and mucosal remodeling. Transcriptomic analysis revealed that HDAC7-low tissues demonstrated enriched type 2 pathways, whereas high expression aligned with TH1/TH17 signatures. In vitro, silencing HDAC7 amplified the broader IL-13-induced transcriptional program and specifically enhanced C-C motif chemokine ligand 26 (CCL26) production, promoting C-C chemokine receptor type 3-dependent eosinophil migration. Notably, this effect appeared specific to HDAC7 loss, as broad-spectrum HDAC inhibition with trichostatin A suppressed CCL26 and did not recapitulate the knockdown phenotype.
CONCLUSION: HDAC7 appears to function as an inducible negative regulator in the nasal epithelium, attenuating IL-13-driven CCL26 production. Disruption of this feedback loop may contribute to exacerbated type 2 inflammation, suggesting epithelial HDAC7 as a potential biomarker and therapeutic target for CRSwNP.
OBJECTIVE: To explore the role of epithelial HDAC7 in restraining excessive inflammation in CRSwNP.
METHODS: Primary human nasal epithelial cells were exposed to inflammatory stimuli to identify HDAC7 inducers. Epithelial HDAC7 expression in patient tissues was correlated with inflammatory markers and remodeling indices. Mechanistic roles were assessed using lentiviral knockdown, transcriptome sequencing, and eosinophil chemotaxis assays.
RESULTS: Interleukin (IL)-13 selectively induced epithelial HDAC7 expression. In clinical tissues, lower HDAC7 expression within the CRSwNP cohort correlated with severe type 2 inflammation and mucosal remodeling. Transcriptomic analysis revealed that HDAC7-low tissues demonstrated enriched type 2 pathways, whereas high expression aligned with TH1/TH17 signatures. In vitro, silencing HDAC7 amplified the broader IL-13-induced transcriptional program and specifically enhanced C-C motif chemokine ligand 26 (CCL26) production, promoting C-C chemokine receptor type 3-dependent eosinophil migration. Notably, this effect appeared specific to HDAC7 loss, as broad-spectrum HDAC inhibition with trichostatin A suppressed CCL26 and did not recapitulate the knockdown phenotype.
CONCLUSION: HDAC7 appears to function as an inducible negative regulator in the nasal epithelium, attenuating IL-13-driven CCL26 production. Disruption of this feedback loop may contribute to exacerbated type 2 inflammation, suggesting epithelial HDAC7 as a potential biomarker and therapeutic target for CRSwNP.